Genetic architecture of immune system

A new study has identified the key genes involved in the breadth of our immune response that may influence our susceptibility to diseases such rheumatoid arthritis, leprosy and malaria. 

The study, led by King's College London and the US National Institutes of Health (NIH), suggests much of our immune system is under the control of our genes and may explain why autoimmune disorders run in some families and others are more susceptible to infections.

Our immune system has evolved over millions of years into a remarkable defence mechanism offering us rapid protection from major environmental threats and pathogens.

However, despite recent discoveries of genetic variants associated with autoimmunity and infection, how our genes control critical components of our immune system has remained poorly understood up to now. 

In the new study, funded by the National Institute for Health Research (NIHR), researchers looked for the first time at the full complexity of the immune cells in a large group of twins, to understand how much of our natural immune defence is controlled by our genes and to identify the key genes. The team used a new NIH method to detect over 30,000 markers of the immune system in each person's blood combined with a million gene markers to explore the link between genetics and immunity in 669 female twins recruited through the TwinsUK study at King's College London.

The study, published in the journal Cell, found over a hundred gene variants associated with different types of white cells all with different immune functions. Each of these findings provides clues as to how the immune system can malfunction and lead to disease or infection. Some of these genes not only control the number of white blood cells, but may also play a potentially important role in our susceptibility to autoimmune diseases such as lupus, rheumatoid arthritis and infectious diseases such as HIV and malaria.

The database created by the study offers a publicly accessible bioresource for researchers to look up genes of interest to better understand the mechanisms of immune-related diseases, and should aid the discovery of novel biomarkers and targeted therapies.

Professor Frank Nestle, co-author from St. John's Institute of Dermatology, King's College London, says, ''Our study shows that our immune system is partly inherited from our parents and ancestors.  This will determine our ability to fight diseases such as HIV or malaria and our susceptibility to autoimmune disease.''

Professor Tim Spector, co-author from the Department of Twin Research & Genetic Epidemiology, King's College London, says, ''Many key parts of our immune system appear to be controlled by our genes, and we can now work to better understand how variations in these genes strengthen or weaken our immunity. This resource should ultimately help clinicians to design more personalised treatments for people with immune problems in the future.''

The study was funded by the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.